Multi-site injection system

ABSTRACT

A multi-site injection system includes a plurality of medicament delivering needles/microprotrusions, a needle/microprotrusion support, a supply of medicament, and a mechanism for providing the medicament to the plurality of needles/microprotrusions in order to effect delivery into a stratum corneum of a user.

The present invention is generally directed to the administration of amedicament and is more particularly directed to a multi-site injectionsystem for dermal delivery of a medicament.

Topical delivery of medicament is a very useful method for achievingboth systemic and localized pharmalogical effects. A problem in suchtranscutaneous drug delivery is providing sufficient drug penetrationacross the skin.

As is well know, the skin consists of multiple layers, starting with astratum corneum layer of about 20 microns for humans, a viable epidermaltissue layer of about 70 microns and a dermal layer of about 2 mm inthickness.

As such, the stratum corneum represents a major barrier for chemicalpenetration through the skin being responsible for the majority of theskin barrier property. This is, of course, dependent upon the medicamentwater solubility and molecular weight.

Delivering medicament through the skin may be attained by piercing thestratum corneum and delivering a drug to the skin in or below thestratum corneum. Such devices for piercing the stratum corneum mayinclude a plurality of micron-sized needles or blades having lengthssufficient to pierce the stratum corneum without passing completelythrough the epidermis. Once a medicament is passed through the stratumcorneum, there typically is no major hindrance to penetration of theremaining epidermal layers or the dermis.

Do to sometimes painful use of individual needle penetration of thestratum corneum, it is desirable to provide a plurality of micro needlesor protrusions for simultaneous delivery of a medicament through alarger area of stratum corneum.

Accordingly, the present invention provides for a multi-site injectionsystem utilizing a plurality of microprotrusions or needles for piercingthe stratum corneum of the skin to a depth sufficient for delivering amedicament through the skin of a patient.

SUMMARY OF THE INVENTION

A multi-site injection system in accordance with the present inventiongenerally includes a plurality of medicament deliveringneedles/microprotrusions along with a support therefore. A supply ofmedicament is provided and a means provided for supplying the medicamentto the plurality of needles/microprotrusions in order to effect deliveryinto a stratum corneum of a user.

One embodiment of the present invention generally includes a rotatabledrum having an outer surface with the microprotrusions thereon.

The microprotrusions may include passages, or lumens, therethrough forenabling transport of the medicament therethrough from an inner surfaceof the rotatable drum and into the stratum corneum of a user.Alternatively the microprotrusions may be solid and coated with themedicament.

A fixed inner drum may be provided for supporting the rotatable drum andincludes at least one radial opening therein for providing themedicament to the microprotrusions.

The supply of medicament is disposed within the inner drum and a housingis provided for supporting the rotatable drum and the inner drum. Thehousing includes an opening for exposing an arcuate portion of therotatable drum in order to enable rotation of the rotatable drum byrolling the rotatable drum against a users skin.

While not shown, a blatter may be provided for containing the medicamentwith the blatter being in fluid communication with the radial opening ina fixed inner drum for providing the medicament to the microprotrusionpassages.

An alternative embodiment of a multi-site injection system in accordancewith the present invention generally includes a guide plate having aplurality of openings therethrough and needle plate having a pluralityof needles projecting therethrough with each needle being aligned with acorresponding opening and a guide plate.

The needle plate is movable from a first position with the needlesposition behind a top surface of the guide plate to a second positionwith the needles projecting from the top plate through the openings. Aplunger base is provided for moving the needle plate from the first tothe second position.

The needles may be coated with a medicament or the needles may includelumens in communication with a medicament reservoir, or supply, disposedin the plunger base for delivery of the medicament into a stratumcorneum of a users skin.

The needles and openings may be arranged in order to applicate themedicament to a users skin in a definite pattern which, may be asymmetrical radial pattern, an asymmetrical radial pattern or aconcentric pattern which may or may not be circular. A rectilinearpattern of needles may be utilized in accordance with the presentinvention and the medicament preferably comprises botulinum toxin.

A further embodiment of a multi-site injection system in accordance withthe present invention generally includes a needle plate and a pluralityof hollow needles fixed to an outside of the needle plate, for transportof a medicament from an inside of the needle plate and into a stratumcorneum of a user.

A pressurizer is provided and disposed over an inside of the needleplate to form a cavity therebetween in communication with the hollowneedles.

In addition, an injection port is disposed in the pressurizer forintroducing the medicament into the cavity.

More particularly, in accordance with the present invention, thepressurizer is flexible for causing uniform transport of the medicamentthrough the needles.

Accordingly, the pressurizer provides a means for forcing the medicamentfrom the cavity through needle lumens.

A still further embodiment of a multi-site manifold injection system inaccordance with the present invention generally includes a handle alongwith a syringe supported by the handle and including a plunger fordispensing a fluid medicament from the syringe.

A manifold is attached to one end of the handle and in fluidcommunication with a syringe and a plurality of needles, protruding fromthe manifold, are provided for delivery of the fluid medicament from themanifold and into the stratum corneum of a user.

In accordance with one embodiment of the present invention, the manifoldmay be disposed perpendicular to the handle and further comprise aplurality of concentric conduits interconnected with radial conduits.

The concentric conduits may be circular and radially spaced apart fromone another.

In addition, a transparent sheet may be provided and interconnecting aconcentric and radial conduits for enabling visual orientation of themanifold onto a patients' skin by manipulation of a handle.

Alternatively, the manifold may comprise a plurality of concentricconduits and a plurality of radial ribs supporting the plurality ofconcentric conduits. Preferably, the medicament utilized in combinationwith the syringe manifold and needle is botulinum toxin.

Yet another embodiment of the present invention includes a multi-siteblister injection system having a carrier sheet including a plurality ofmedicament filled rupturable blister disposed on an inside surfacethereof.

A plurality of needles extending from the outside of the carrier streammay be provided with each needle being aligned with a correspondingblister and having a lumen for transport of the medicament into thestratum corneum of the user.

Each of the needles is positioned for traversing the carrier sheet andrupturing the corresponding blister.

A pressure plate is disposed on the carrier sheet inside surface forforcing a blister against the needles for causing rupture thereof andforcing a medicament through the needle lumens.

The pressure plate may be fixed to the carrier sheet and a foam pad maybe disposed on the carrier sheet outside. Preferably, the foam padcovers the needles extending the carrier sheet outside and is penetrableby the needles.

The foam pad may be adhered to the pressure plate along a perimeterthereof for securing the carrier sheet between the foam pad and thepressure plate.

Preferably, the medicament in accordance with the present inventioncomprises botulinum toxin.

Still another embodiment of a multi-site injection system in accordancewith the present invention generally includes a shell including a topand a bottom and a plurality of needles protruding from the shellbottom. Each of the needles include a lumen extending through the shellbottom.

A membrane is provided and disposed between the shell top and the shellbottom and an inlet is provided for introducing a fluid between theshell top and the shell bottom.

A diverter is also provided for selectively directing fluid between themembrane and the shell bottom and between the membrane and the shelltop.

The diverter may include a manually operated valve and the system mayfurther include the supply of medicament, preferably botulinum toxin,for introduction between the membrane and the shell bottom.

An inert fluid supply may also be provided for introduction between themembrane and the shell top.

Also in accordance with the present invention, a method of multi-siteinjection comprises providing a shell between the top and a bottom withbottom having a plurality of needles protruding therefrom with eachneedle including a lumen therethrough and extending through the shellbottom.

The method also includes providing a membrane between the shell top andthe shell bottom.

More particularly, in accordance with the present invention, the methodincludes introducing a medicament between the membrane and the shellbottom and introducing a pressurized fluid between the membrane and theshell top for forcing the medicament through the needle lumens.

The medicament in accordance with the present invention preferablycomprises botulinum toxin.

BRIEF DESCRIPTION OF THE DRAWINGS

The advantages and features of the present invention will be betterunderstood by the following description when considered in conjunctionwith the accompanying drawings in which:

FIG. 1 is a perspective view of a multi-site injection system inaccordance with the present invention generally showing a housing, orshell, for supporting a rotatable drum along with a rotatable drumhaving an outer surface with microprotrusions therein, a port is alsoshown which provides an access for charging the system with a medicamentto be injected, such as, for example botulinum toxin;

FIG. 2 is a partial cross section of the system shown in FIG. 1 moreclearly illustrating a fixed inner drum for containing a medicament andat least one radial opening therein for providing medicament to aplurality of microprotrusions affixed to and rotatable with therotatable drum, the rotatable drum is rotated by rolling the drumagainst a users skin, not shown, and the housing supporting therotatable drum and the inner drum includes an opening for exposing anarcuate portion of the rotatable drum for enabling rotation thereof;

FIG. 3 is a cross sectional view taken along line 3-3 of FIG. 2 moreclearly showing operation of the system;

FIG. 4 is a perspective view of a multi-site injection system inaccordance with the present invention generally showing a guide platehaving a plurality of openings therethrough, a plunger base and aplurality of needles projecting from the guide plate;

FIG. 5 is a partial cross section of one embodiment of the presentinvention showing a reservoir of medicament disposed in the plunger basewith needle lumens in fluid communication therewith and disposed withneedle points generally flush with a top surface of the guide plate;

FIG. 6 is a cross sectional view similar to that shown in FIG. 5illustrating movement of the plunger base for protruding the needlesfrom the top surface of the guide plate and into a stratum corneum of ausers skin;

FIG. 7 illustrates continued pressure on the plunger base for forcingmedicament through the needle lumens and into the stratum corneum of theusers skin;

FIGS. 8 and 9 illustrate various needle patterns which may be suitablefor various applications and areas of treatment on a users skin;

FIG. 10 is a perspective view of a multi-site injection system inaccordance with the present invention generally showing a needle platewith a plurality of needles projecting therefrom and fixed to an outsidesurface of the needle plate;

FIG. 11 is a perspective view of the multi-site injection system shownin FIG. 0.1 showing a reverse side with a pressurizer disposed over aninside of the needle plate along with an injection port and apressurized reservoir of medicament interconnected to the port via atube;

FIG. 12 is a partial cross section of the injection system shown inFIGS. 10 and 11 illustrating a cavity for and between the pressure plateand an inside surface of the needle plate illustrating medicament flowfrom the pressure reservoir through the tube into the cavity and throughhollow needles for transport of the medicament into a stratum corneum ofa user;

FIG. 13 is a perspective view of the multi-site manifold injectionsystem in accordance with the present invention generally showing ahandle, a manifold attached to one end of the handle and a plurality ofneedles protruding from the manifold for delivery of fluid medicamentfrom the manifold into a stratum corneum of a user, not shown;

FIG. 14 is a cross sectional view of the system shown in FIG. 13 moreclearly shown a syringe supported by the handle and including a plungerfor dispensing the fluid medicament from the syringe;

FIG. 15 is a perspective view of a multi-site blister injection systemin accordance with the present invention generally showing a carriersheet and a pressure plate disposed on an inside surface of the carriersheet;

FIG. 16 is an exploded perspective view of the system more clearlyillustrating a carrier sheet with medicament filled blisters and a foampad;

FIG. 17 is a cross sectional view of the embodiments shown in FIGS. 15and 16 more clearly illustrating a plurality of needles extending fromthe carrier sheet, a plurality of rupturable blisters filled with amedicament, such as botulinum toxin, along with the pressure platepositioned for forcing the blisters against corresponding needles forcausing rupture thereof and forcing medicament through needle lumens;

FIG. 18 is a cross sectional view similar to that shown in FIG. 17 inwhich the pressure plate has been forced against the blisters andmedicament is forced into the stratum corneum of a users skin;

FIG. 19 is a perspective view of a multi-site injection system inaccordance with the present invention generally illustrating a shellhaving a top and a bottom with a plurality of needles protruding fromthe shell bottom. An inlet for introducing fluid between the shell topand bottom is shown along with a diverter;

FIG. 20 is a cross sectional view of the system shown in FIG. 19 moreclearly illustrating the shell top, bottom and a membrane disposedbetween the shell top and the shell bottom along with a diverter valvefor selectively directing fluid between the membrane and the shellbottom and between the membrane and the shell top, FIG. 20 showing afilling cycle with medication being injected into a reservoir;

FIG. 21 is a cross sectional view similar to FIG. 20 showing thediverter selectively directing fluid between the membrane and top shellduring an injection cycle in order to pressurize the reservoir ofmedicament thereby forcing the medicament through needle lumens; and

FIG. 22 is an enlarged view of the needles illustrating a lumentherethrough for injection of the medicament into the stratum corneum ofa users skin (not shown).

DETAILED DESCRIPTION

With reference to FIG. 1, there is shown a multi-site injection system10 which includes a rotatable drum 12 including an outer surface havinga plurality of microprotrusions, or needles, affixed thereto. Themicroprotrusions may have lumens, or passages, therethrough.

A housing 20 is provided for supporting the rotatable drum along with afixed inner drum 24, see FIGS. 2 and 3. An arcuate opening 28 in thehousing 120 is provided for exposing the drum surface 14 which enablesrotation of the drum 12 by rolling the drum 12 against a users skin 42.

Also shown in FIG. 1 is an access 34 which is provided for introducing amedicament, such as botulinum toxin into the system via a syringe, notshown, or other suitable conveyance.

As more clearly shown in FIGS. 2 and 3, an inner drum, fixed to thehousing, or shell, 20, is provided for containing a supply of medicamentinstilled through the access port 30 as hereinabove noted.

This nonrotating inner drum, or reservoir, 36 includes a plurality ofradial passages, or openings, 38 for providing the medicament 36 to theneedles 18.

Preferably, a sponge-like material 40 is disposed on the rotatable drum12 for both distributing medicament provided through the radial openings18 and enabling application of the medicament via the needles 18 withoutexcess medicament being deposited on the users skin 42.

In operation, rotation of the drum 12 on the users skin 42 causesrotation of the drum as indicated by the arrow 44 and medicament flowsinto the sponge and is applied to the users skin 42. The needlespenetrate the stratum corneum, or skin, 42 of the user, thus introducingthe medicament thereinto.

Alternatively, the protrusions, or needles may include lumenstherethrough for direct transport of medicament 36 from the inner drum34 upon rotation of the drum 12 against the users skin 42.

With reference to FIG. 4, there is shown an injection system 110generally including a guide plate 112 having a plurality of openingstherethrough along with a needle plate 120 including a plurality ofneedles 124 shown extending through the openings 116 and projecting froma top surface 128 of the guide plate 112. Also shown is a plunger base130 for moving the needle plate from a first position with the needles124 positioned generally behind the top surface 128, see FIG. 5 to asecond position with the needles 124 projecting from the top surface 128as shown in FIGS. 4, 5, and 6.

The needles 124 may be coated with a medicament, such as, for example,botulinum toxin.

The guide plate 112, needle plate 120, needles 124, and base 130 may bemade form any suitable material and the needles preferably are about 128gauge and 1 mm in length. Use of the multi-site injection system 110 fordelivery of a medicament into the stratum corneum of a users skin isillustrated in FIGS. 5-7.

As shown, the needle plate is configured in any suitable manner forbeing moveable from a first position shown in FIG. 5 with the needlespositioned behind, or flush with the top surface 128 of the needle plate120 to a second position shown in FIGS. 6 and 7 with the needles 124projecting from the top surface 128 through the openings 116.

The plunger base 130 preferably includes and defines a reservoir 142between the needle plate 120 and the base 130 for containing themedicament 134.

Incompressibility of the medicament 134 enables movement of the plungerbase 130 to move the needle plate 120 from the first to the secondposition as indicated by the arrows 146.

Continued movement of the plunger base 130 forces medicament 134 throughneedle lumens 150 and collapse of the reservoir 142. The guide plate112, needle plate 120, and plunger based 130 may be integrally formedwith a diaphragm arrangement, not shown, for enabling the relativemotion hereinabove described. Other suitable configurations should beconsidered to be within the scope of the present invention.

It should be appreciated that while the system 110 shown in FIG. 4illustrates, holds, or openings 116 and needles arranged in a generallysymmetrical radial pattern, other patterns may be utilized for deliveryof a medicament to body areas requiring different patterns ofapplication. FIGS. 8 and 9 illustrate systems 154, 156 showing anasymmetrical radial pattern and a rectilinear pattern respectively.

With reference now to FIGS. 10 and 11, there is shown a multi-siteinjection system 208 in accordance with the present invention generallyincluding a flexible needle plate 210 having a plurality of hollowneedles 212 fixed to an outside surface 216 of the needle plate 210. Theneedle plate 210 may be formed from any suitable material and theneedles may be formed thereinto or affixed thereto in any conventionalmanner.

As more clearly shown in FIG. 11, the system 208 may include apressurizer 220, which may be in the form of a flexible blatter or thelike, for causing uniform pressure across an inside surface 224 of theneedle plate 210.

As shown in FIG. 12, the pressurizer 220 establishes a cavity 226between the pressurizer 220 and the inside surface 224 of the needleplate 210.

As shown in FIG. 12, the inside surface 224 of the needle plate 210 mayinclude a separate containment element 228 to facilitate construction ofthe system 208. Thus, as illustrated the pressurizer 220 provides ameans for forcing medicament, which is preferably botulinum toxin fromthe cavity 226 through needle lumens 232. Spacing and orientation of theneedles on the needle plate 210 is determined by the intended use of theneedle plate 210 on specific user body parts, not shown.

An injection port 234 is preferably interconnected to a pressurereservoir 236 through a tube 240. Control of medicament flow from thepressure reservoir 236 through the tube and into the cavity 226 may becontrolled in any conventional manner.

Pressure medicament in the cavity 226 thus forces the medicament into astratum corneum 242 of a user, not shown.

Pressure provided by the flexible pressurizer as indicated by the arrows244, 246 enable uniform flow of medicament as indicated by arrows 248,250 through the needle lumens 232 as indicated by arrows 252, 254.

With reference to FIGS. 13 and 14, there is shown a multi-site injectionsystem 310 including a handle 312, a syringe 316, which includes aplunger 318 for dispensing a fluid medicament from the syringe and intoa manifold 322, as illustrated by arrows 326 in FIG. 14.

The handle 312, syringe 316, plunger 318, and manifold 322 may be formedby any suitable materials. As shown in FIGS. 13 and 14, the manifold 322may be disposed in a generally perpendicular relationship with thehandle 312 and plunger 318 and a plurality of needles 330 protrudingfrom the manifold 322 for delivery of fluid medicament from the manifold322 into a stratum corneum of a user (not shown).

The needles may be affixed to the manifold 322 in any conventionalmanner may be approximately 328 gauge with a length of approximately 1mm and include needle lumens 334 in fluid communication with conduits338 of the manifold 322. The conduits may be concentric and in fluidcommunication with radial members 342.

In one embodiment of the present invention, the radial members may behollow for providing fluid communication of medicament or alternativelyin another embodiment of the present invention may be solid ribs forsupporting the conduits 338.

A transparent sheet 346 may interconnect the conduits 338, 342 forenabling a constant pressure to be exerted over the entire areapresented by the manifold 322 while enabling visual orientation of themanifold 322 onto a patients' skin (not shown) by manipulation of thehandle 312.

In operation, finger pressure on the plunger 318 drives, or otherwiseratchets, a piston 350 disposed within the syringe for forcingmedicament 354 downwardly through an exit port 356 and into the manifoldconduits 338, as hereinabove noted, forcing medicament through theneedle lumens 334 as indicated by the arrows 360. It should beappreciated that any suitable plunger, syringe, which may be fitted intothe handle of the present invention is to be considered within the scopeof the present invention.

With reference to FIGS. 15 and 16, there is shown a multi-site injectionsystem 410 in accordance with the present invention showing a carriersheet 412 along with a foam pad 414, see FIG. 16. A pressure plate 416is disposed on a carrier sheet inside surface 420 and the foam pad 414may include an adhesive for holding the carrier sheet 412 against thepressure plate 416.

With reference to FIGS. 17 and 18, the carrier sheet 412 may be ofconventional design and include blisters 424 filled with a medicament426 as well as a plurality of protruding needles 430 extending from anoutside surface 432 of the carrier sheet 412. Each of the needles whichmay be, for example, 428 gauge and having 2 mm length and include lumens436 for transport of medicament therethrough.

Each of the needles 430 is aligned with a corresponding blister 424 andeach needle including a point 438 for rupturing of correspondingblisters 424.

As shown, the pressure plate preferably includes a plurality of berms440 for providing enhanced pressure against blisters as the pressureplate 416 is forced against the blisters 424.

The foam pad 414 preferably has a depth equal to or slightly greaterthan the length of the needles 430 in order to prevent inadvertentcontact with the needles before use.

In operation, as shown in FIG. 18, when the pressure plate 416 is forceddownwardly as indicated by the arrows 444, the needle points 438 arerupture the blisters 424 and continued pressure by the pressure plate416 collapses the blisters 424 and forces medicament through the needlelumens 436 as indicated by the arrows 442.

This pressure also compresses the foam pad 414 as shown against a usersskin 444 and into the stratum corneum 446. It should be appreciated thatthe drawings are not to scale but rather enlarged to illustrate theoperation of the multi-site injection system 410.

With reference to FIGS. 19-22, there is shown a multi-site injectionsystem 510 in accordance with the present invention generally includinga shell 512 having a top 516 and a bottom 518. A plurality of needles522 protrude from the shell bottom 518 with each needle 522 including alumen 524 (see FIG. 22) communicating with a reservoir 526 establishedby a membrane 528 disposed between the shell top 516 and the shellbottom 518.

It should be appreciated that the shell, membrane and needles may bemade from any suitable material. Preferably, the needles have a gauge ofabout 528 and a length in the order of 2 mm. An inlet 530 including atube 532 and passageway 534 provide a means for introducing a fluidbetween the shell top 516 and shell bottom 518.

A diverter 538 includes a manually operated valve 540 for selectivelydirecting fluid between the membrane 528 and shell bottom 518 into thereservoir 526.

As shown by the arrow 544 during a filling cycle the inlet, or supplyline, introduces a medicament, preferably botulinum toxin, into thereservoir by alignment with a dip tube 548 with the passageway 534 forfilling of the reservoir 526.

Thereafter, the diverter 538 by way of the valve 540 aligns thepassageway 534 for introducing a fluid, such as saline solution, betweenthe membrane 528 and the top shell as illustrated by the arrows 552,554. This provides a pressure above the membrane 528 which forces themedicament from the reservoir 526 through the needle lumens 524 asillustrated by the arrows 558.

Although there has been hereinabove described various multi-siteremotely pressurized injection systems in accordance with the presentinvention for the purpose of illustrating the manner in which theinvention may be used to advantage, it should be appreciated that theinvention is not limited thereto. That is, the present invention maysuitably comprise, consist of, or consist essentially of the recitedelements. Further, the invention illustratively disclosed hereinsuitably may be practiced in the absence of any element which is notspecifically disclosed herein. Accordingly, any and all modifications,variations or equivalent arrangements which may occur to those skilledin the art, should be considered to be within the scope of the presentinvention as defined in the appended claims.

1-51. (canceled)
 52. A multi-site injection system comprising: a guideplate having a plurality of openings therethrough; a needle plate havinga plurality of needles projecting therefrom, each needle being alignedwith a corresponding opening in said guide plate, said needle platebeing movable from a first position with the needles positioned behind atop surface of said guide plate to a second position with the needlesprojecting from the top surface through the openings; and a plunger basefor moving said needle plate from the first to the second position. 53.The system according to claim 52 wherein said plunger bore includes areservoir for medicament and needles include lumen therethrough incommunication with said reservoir for delivery of the medicament into astratum corneum of a user's skin.
 54. The system according to claim 52wherein the needles and opening are arranged in a symmetric radialpattern.
 55. The system according to claim 52 wherein the needles andopening are arranged in an asymmetric radial pattern.
 56. A multi-siteinjection system comprising: a handle; a syringe supported by saidhandle and including a plunger for dispensing a fluid medicament fromsaid syringe; a manifold attached to one end of said handle and in fluidcommunication with said syringe; a plurality of needles, protruding fromsaid manifold, for delivery of said fluid medicament from said manifoldand into a stratum corneum of a user.
 57. The system according to claim56 wherein said manifold is disposed perpendicular to said handle. 58.The system according to claim 56 wherein said manifold comprises aplurality of concentric conduits interconnected with radial conduits.59. The system according to claim 56 wherein the concentric conduits areradially spaced apart from one another.
 60. The system according toclaim 59 further comprising a transparent sheet interconnecting theconcentric and radial conduits for enabling visual orientation of saidmanifold onto a patient's skin by manipulation of said handle.
 61. Amulti-site injection system comprising: a shell including a top and abottom; a plurality of needles protruding from the shell bottom, eachneedle including a lumen extending through the shell bottom; a membranedisposed between the shell top and shell bottom; an inlet forintroducing a fluid between the shell top and the shell bottom; and adiverter for selectively directing fluid between the membrane and theshell bottom and between the membrane and the shell top.
 62. The systemaccording to claim 61 wherein said diverter includes a manually operatedvalve.